Leadless tissue stimulation systems and methods

ABSTRACT

Systems including an implantable receiver-stimulator and an implantable controller-transmitter are used for leadless electrical stimulation of body tissues. Cardiac pacing and arrhythmia control is accomplished with one or more implantable receiver-stimulators and an external or implantable controller-transmitter. Systems are implanted by testing external or implantable devices at different tissue sites, observing physiologic and device responses, and selecting sites with preferred performance for implanting the systems. In these systems, a controller-transmitter is activated at a remote tissue location to transmit/deliver acoustic energy through the body to a receiver-stimulator at a target tissue location. The receiver-stimulator converts the acoustic energy to electrical energy for electrical stimulation of the body tissue. The tissue locations(s) can be optimized by moving either or both of the controller-transmitter and the receiver-stimulator to determine the best patient and device responses.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 11/315,023(Attorney Docket No. 021834-000820US), filed on Dec. 21, 2005, whichclaims the benefit and priority of the following: U.S. ProvisionalApplication No. 60/689,606 (Attorney Docket No. 021834-000810US), filedon Jun. 9, 2005; U.S. Provisional Application No. 60/639,027 (AttorneyDocket No. 021834-000800US), filed on Dec. 21, 2004; and U.S.Provisional Patent Application No. 60/639,037 (Attorney Docket No.021834-000900US), filed on Dec. 21, 2004, the full disclosures of whichare incorporated herein by reference.

The subject matter of this application is also related to that ofapplication Ser. No. 11/315,524 (Attorney Docket No. 021834-001010US),filed on Dec. 21, 2005, which claims the benefit of ProvisionalApplication No. 60/639,056 (Attorney Docket No. 021834-001000US), filedon Dec. 21, 2004, the full disclosures of which are incorporated hereinby reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The systems and methods of this invention relate to electricalstimulation of the heart and other body tissues by means of animplantable device. Specifically the present invention relates tosystems and methods for providing such stimulation without the use ofconventional lead/electrode systems. More specifically, the presentapplication provides systems and methods for treatment of heart failureand for terminating heart arrhythmias with implantable pacing systemsand components.

Electrical stimulation of body tissues is used throughout medicine fortreatment of both chronic and acute conditions. Among many examples,peripheral muscle stimulation is reported to accelerate healing ofstrains and tears, bone stimulation is likewise indicated to increasethe rate of bone regrowth/repair in fractures, and nerve stimulation isused to alleviate chronic pain. A commonly implanted device utilizingelectrical stimulation is the cardiac pacemaker. Further there isencouraging research in the use of electrical stimulation to treat avariety of nerve and brain conditions, such as essential tremor,Parkinson's disease, migraine headaches, functional deficits due tostroke, and epileptic seizures.

Devices to provide such stimulation may be applied externally in somecases, or in other cases it is more advantageous to implant all or partof the device. This invention pertains to devices in which at least oneportion providing direct electrical stimulation to the body tissue iseither permanently or temporarily implanted. Such devices includepacemakers, implantable defibrillators, and other devices forstimulating cardiac and other tissues.

Electrical energy sources connected to electrode/lead wire systems havetypically been used to stimulate tissue within the body. The use of leadwires is associated with significant problems such as complications dueto infection, lead failure, and electrode/lead dislodgement.

The requirement for leads in order to accomplish stimulation also limitsthe number of accessible locations in the body. The requirement forleads has also limited the ability to stimulate at multiple sites(multisite stimulation). For instance, the treatment of epilepsy couldrequire a minimum of perhaps 5 or 6 stimulation sites. Other diseases,such as Parkinson's disease, would benefit from more stimulation sitesthan the two utilized in current systems.

Beyond the problems of outright failure and placement difficulties,pacemaker leads inherently cause problems for pacemaker systems byacting as antennae, coupling electromagnetic interference (EMI) into thepacemaker electronics. Particularly problematic is interference withcardiac electrogram sensing and signal processing circuitry. With theexponential rise in the number of cellular telephones, wireless computernetworks, and the like, pacemaker lead induced EMI will continue to spurincreased complexity in the design of, and require significant testingof pacemaker devices.

The most commonly implanted stimulation device is the cardiac pacemaker.A pacemaker is a battery-powered electronic device implanted under theskin, connected to the heart by an insulated metal lead wire with a tipelectrode. Pacemakers were initially developed for and are most commonlyused to treat bradycardia, slow heart rates, which may result from anumber of conditions. More recently, advancements in pacemakercomplexity, and associated sensing and pacing algorithms have allowedprogress in using pacemakers for the treatment of other conditions,notably heart failure (HF) and fast heart rhythms(tachyarrhythmia/tachycardia).

In a common application, pacemaker leads are placed through the skininto a subclavian vein or branch to access the venous side of thecardiovascular system. Such systems can be either single chamber with alead placed in either the right atrium or right ventricle, or dualchamber systems with one lead placed in contact with the right atrialwall and a second lead placed in contact with the right ventricularwall. For the treatment of HF, through what is commonly known as cardiacresynchronization therapy, bi-ventricular pacing is utilized, requiringthat an additional lead be placed in contact with the left ventricle. Toaccess the left ventricle, the third lead is typically advanced into theright atrium, into the orifice of the coronary sinus, and thenmaneuvered through the coronary sinus veins to a position on theepicardial aspect of the posterolateral or lateral wall of the leftventricle.

Though now less common after nearly five decades of improvement indesigns and materials, failure of a pacemaker lead is still asignificant risk to the patient not only for the loss of pacing whichmay represent a life-threatening event, but also due to the fact thatonce implanted, pacemaker leads are only extracted with a procedure orsurgery of significant risk. Additionally, the location of an existingnon-functional lead, if not removable, may prevent implantation of areplacement lead. Pacemaker leads may fail due to a number of reasonsincluding breakage of the insulator or conductor and loose orincompatible connectors.

In biventricular pacing for HF, placement of the third lead to contactthe left ventricle remains a significant problem. The coronary sinus isa complicated venous pathway with multiple branches which bend andnarrow with considerable variation as they extend distally onto theepicardium of the left ventricle. Placement of the third lead requiressignificant skill on the part of the physician. In order to provideadequate steerability and pushability, the design of the leftventricular lead or a lead introduction system/device is much morecomplicated than regular pacing leads. Often the positioning andplacement of the left ventricular lead can take over an hour to perform,exposing the patient to increased fluoroscopy radiation and increasedprocedure risks. In some patients (7.5% in the MIRACLE study) anacceptable lead placement is not possible due to anatomic constraints orphrenic nerve pacing. Additionally, lead dislodgement and loss of pacinghave been common complications in the use of these coronary sinus leads(10-20% complication rates within the first 6 months of deviceplacement).

The requirement for a lead to accomplish left ventricular stimulationlimits the placement to either the coronary sinus vein as describedabove or an epicardial placement which uses surgical techniques to placethe lead on the epicardium and then tunneling of the lead to thelocation of the pacing device for connection. Left ventricular leads arenot placed inside the heart chamber as they are for the right-sidedleads for several reasons. They would have to be chronically situatedretrograde across the aortic valve or transeptally across the mitralvalve which could cause aortic or mitral valvular insufficiency. Thepatients would be subject to risk of thromboembolic complications fromhaving leads in the arterial circulation. Retrograde insertion of apacing lead into the left ventricle via the aorta would require apermanent arterial puncture for lead insertion, permanent aorticregurgitation, and permanent anticoagulation to prevent thrombusformation. Alternatively, atrial transeptal puncture from the rightatrium to insert a pacing lead into the left atrium or left ventriclealso requires permanent anticoagulation, and for left ventricular sites,would cause mitral regurgitation. Moreover, all pacemaker leads areassociated with an incidence of infection, and the risk of valvularendocarditis is greater in the left heart.

In patients receiving a bi-ventricular pacing system, site selection forplacement of the left ventricular lead has been found to be criticallyimportant in order to provide hemodynamic benefit. Up to 40% of patientsreceiving bi-ventricular pacing for the treatment of HF do not benefit(i.e. hemodynamic measures and HF functional class do not improve ordeteriorate). The most important cause for lack of benefit is thought byexperts to be due to suboptimal or incorrect left ventricularstimulation site. However, restrictions imposed by the difficulty ofpositioning and by the anatomy of the coronary sinus and its branchesoften limit the ability to select a more optimal left ventricular pacingsite. The ability to precisely select the left ventricular site forstimulation in combination with right ventricular stimulation, would aidin the treatment of HF.

Moreover, left ventricular stimulation currently is restricted to siteson the epicardial (outer) surface of the heart; the coronary sinuscourses on the epicardium, and surgically implanted left ventricularleads are screwed into the epicardium. Recent data indicates thatendocardial (inside lining) or subendocardial (inside layer) stimulationsites in the left ventricle provide additional benefit.

Importantly, clinical trial data now suggest that pacing of the leftventricle alone may result in hemodynamic benefit equivalent to that ofbi-ventricular pacing. Thus, a leadless pacing system has the potentialto accomplish the benefit of bi-ventricular pacing without the need fora right ventricular pacing lead or electrodes.

It would also be beneficial to provide more physiological rightventricular pacing for patients without HF. In normal physiology, theright ventricle is first stimulated in the upper septal area, and thenthe impulse travels down specially conducting pathways to the rightventricular apex. However, pacing the right ventricle is virtuallyalways accomplished from a lead tip electrode located in the rightventricular apex, such that the subsequent conduction pathway isabnormal and slow. Clinical trials have recently shown that in patientswith and without A-V block, pacing from the right ventricular apex canresult in increased total mortality and re-hospitalization for heartfailure. Thus it would be advantageous to be able to pace the rightventricle at more physiological locations such as the upper septum. Themost physiological location to pace the ventricle in patients with sinusnodal or A-V junction conduction disease is to directly pace the Hisbundle. However, this location is very difficult to access from thesuperior (vena cava) approach mandated by lead-based systems that attachto a pectorally implanted pulse generator. It would be beneficial todeliver electrodes from the inferior (vena cava) approach via thefemoral veins, in which catheter positioning in the A-V junction regionis known to be easier. For instance, in a published series of permanentHis bundle pacing, the His bundle was first identified using a temporarycatheter inserted via the femoral vein, and this catheter was left inplace to mark the location to target the site to implant the permanentpacing lead. In patients with lower conduction disease involving the A-Vjunction or bundle branches, the most physiological pacing sites havebeen found to be the left ventricular septum or left ventricular apex.These are locations in proximity to the specialized Purkinje conductionnetwork. These locations are not accessible using current transvenouslead-based pacing systems. It would be advantageous to be able to selectthe pacing site in order to model more normal conduction.

Still another advantage of a leadless pacemaker system would beincreased compatibility with magnetic resonance imaging (MRI). Currentpacemaker pulse generators are made of materials and/or containshielding that is generally compatible with the high static andalternating magnetic fields of MRI. However, lead wires are typicallyconstructed with coiled metallic conductors, which are subject toinduced currents from the magnetic field. Such currents can causeunwanted stimulation of the heart, and potentially damage the pacemakerpulse generator. A leadless pacemaker system will obviously eliminatethe problem of current induced in the lead wires, though propermaterials selection and shielding will still have to be employed in thedesign of the implantable components.

Recently, the concept of a leadless, subcutaneous implantabledefibrillator has been proposed e.g. U.S. Pat. No. 6,647,292 (Bardy). Inthis concept high energy electrical waveforms are delivered betweenelectrodes implanted in subcutaneous chest regions creating sufficientenergy density within the thoracic volume to terminate ventriculartachycardia (VT) or ventricular fibrillation (VF). This uses the sameelectrical field density concept for VT/VF termination as externalapplication or as implanted defibrillator devices with electrodes onleads in the heart. In external defibrillation, energy is deliveredbetween electrodes on the skin surface. In this subcutaneous approachelectrodes are implanted beneath the skin but not in contact with theheart. In common implantable systems one of the defibrillationelectrodes may consist of the metal enclosure of the implantedcontroller with the other electrode a coil on a lead placed in the rightside (right ventricle) of the heart.

The subcutaneous implantable defibrillator system has no direct contactwith cardiac tissue so there are added difficulties incorporating pacingtherapy compared to lead-based pacemakers. To pace with subcutaneouselectrodes, a sufficient electrical field must be created between twoelectrodes across the chest volume in order to reach pacing stimulationthresholds in the heart. This method also has no capability to preciselylocalize the electrical effect in the heart. Since this is a fieldeffect, all muscles and nerves in the chest are exposed to theelectrical field. The pacing pulse energy levels required to stimulatecardiac tissue using this electrical field approach are sufficientlyhigh that chest muscle contractions and pain sensations would beassociated with subcutaneous pacing. While pain occurs with high energydefibrillating discharges of all implantable defibrillators, no painoccurs with low-energy pacing using intracardiac leads. A subcutaneouslyimplanted device implementing pacing would cause patient pain and wouldnot be accepted when compared to a pain-free alternative. It would behighly advantageous to have a leadless system that would be capable ofhigh energy defibrillation and also contain painless pacing capability.

In addition to using high energy electrical waveforms for thetermination of VT/VF, lead-based implantable defibrillator systemstypically also contain pacing algorithms that are effective interminating VT/VF, referred to as antitachycardia pacing (ATP). For ATP,both the lead-based implantable system and the leadless subcutaneoussystem concepts have limitations in selecting the location of the pacingapplication, particularly in the left side of the heart. VT can bereadily terminated using low voltage pacing stimulation if the site ofthe pacing is near the ventricular tachycardia focus or reentrantcircuit. However, this is usually in the left ventricle, and close tothe endocardium. As noted above, current pacemaker/defibrillator devicesincorporate antitachycardia pacing but the pacing site is limited to theright ventricular lead or is subject to the same limitations previouslydescribed for left-sided lead placements. Further, right-sided locationshave been shown to be less effective in electrophysiology laboratorytesting, especially for VT's of high rate which are more serious. Pacingstimuli must stimulate cardiac tissue in the excitable region (excitablegap) of the VT reentry circuit in order to terminate the VT. Most VTcircuits are located in the subendocardial layer of the left ventricle.For more rapid rate VT's, the excitable gap is small and the pacingstimuli must be very close to the VT reentry circuit for successful VTtermination. In current pacemaker/defibrillator devices, ifantitachycardia pacing is ineffective in terminating VT, painful highenergy electrical field shocks are delivered. Therefore, it would beadvantageous to be able to select the pacing site, particularly near theendocardium and in the left ventricle. Having the capability to selectthe location for a left ventricular lead for terminating episodes ofventricular tachycardia using antitachycardia pacing techniques would beexpected to be more effective compared to current devices.

Another limitation of both the requirement of having leads and of havinglimited access to the left heart is in the emerging area of multisitepacing for termination of atrial and ventricular fibrillation. Thesearrhythmias typically arise in and are maintained by the left atrium andleft ventricle. Studies have demonstrated the presence of excitable gapswithin the tissue during atrial fibrillation (animal and human studies)and ventricular fibrillation (animal studies). By placing andstimulating at multiple pacing sites, regional pacing capture can beobtained during these arrhythmias. This means that if stimulation isdelivered at the appropriate timing to a sufficient number of sites, inthe appropriate locations, termination of atrial and ventricularfibrillation is possible. The advantage of terminating fibrillation withselected site left ventricular pacing would be the avoidance of painfulhigh energy shocks. In this application the capability for left-sidedstimulation and multi-sites of stimulation would be advantageous.

In addition to the termination of tachyarrhythmias, implanted pacemakersand defibrillators have been used to prevent tachyarrhythmias. Inpatients receiving permanent pacemakers, the dual chamber (DDD) mode hasbeen shown to result in fewer episodes of AF compared to single chamber(VVI) mode in several large clinical trials. DDD pacing thatincorporates simultaneous multisite stimulation of both the high rightatrium and CS ostium has also been compared to standard single atrialsite DDD pacing for the suppression of AF, showing a modest reduction ofAF episodes. Atrial stimulation at a site or multiple sites other thanthe usual right atrial appendage may be advantageous for the preventionof atrial fibrillation by shortening total atrial activation time. Rightatrial sites in Koch's triangle and Bachman's bundle may reduce atrialactivation time by stimulating near or within atrial conduction tractsor within other tracts that are part of the normal conduction pathway.In an experimental canine model (Becker), either 4 pacing sites (2 in RAand 2 in LA) or one in the interatrial septum were required forsuppression of AF. While these results are very promising, they presenta technical obstacle for current pacemaker systems. The use of multisitepacing incorporating pacing sites in the left atrium for the suppressionof AF has not been evaluated in humans because of all the issues ofusing multiple leads and in using leads within the left heart.

It follows that if AF may be able to be suppressed with multisite atrialpacing (especially in the left atrium), that VF may be able to besuppressed with multisite ventricular pacing (especially in the leftventricle). However, the difficulties associated with the implantationof multiple leads in the left ventricle has rendered this form ofprevention impossible.

For these reasons, it would be desirable to accomplish stimulationwithout the need for lead wires. In this application we describe methodsand apparatus, using acoustic energy for an implantable leadlessstimulator system, that overcome limitations in pacing site selection.In co-pending applications we further describe improved stimulatingdevices. Methods and systems to evaluate and optimize positioning forimplantation of this invention are described herein.

2. Description of the Background Art

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BRIEF SUMMARY OF THE INVENTION

The present invention provides methods and devices to electricallystimulate cardiac muscle and other body tissue utilizing acoustic energyto transmit both energy and signal information from a first implanteddevice to a second implanted device. The first implanted device,generally referred to as the controller-transmitter or acousticcontroller-transmitter, provides appropriate timing and controlfunctions and transmits acoustic energy to the second device. The secondimplanted device, generally referred to as the receiver-stimulator,receives the acoustic energy and converts it into electrical energy andapplies that electrical energy to stimulating electrodes. The seconddevice is adapted to be permanently implanted at a location where it isdesired to provide electrical stimulus, with stimulating electrodes indirect contact with the cardiac muscle or other body tissue. Optionally,two or more receiver-stimulators may be implanted to be controlled by asingle controller-transmitter.

A cardiac pacemaker (or defibrillator/cardioversion unit as describedbelow) employing ultrasonic energy transfer according to the presentinvention comprises an implantable receiver-stimulator device adapted tobe implanted in or attached to any desired location eitherendocardially, epicardially, or intramyocardially. Various minimallyinvasive, transvascular techniques and tools (e.g. catheters, stylets)would be adapted and used to deliver, place, embed, and secure thereceiver-stimulator device to these locations. The receiver-stimulatorwould additionally be adapted to provide permanent attachment to theimplant site including possibly the use of helical coils, barbs, tines,clips, or the like. Chronic endothelialization would be encouraged bydesign features such as tines or irregularities in surface, or bybonding onto its outer surface materials which are known to stimulatecellular growth and adhesion. Alternatively, the receiver-stimulatorcould be adapted for implantation in the coronary vasculature atpreferred sites for stimulation, e.g., being incorporated into astent-like platform suitable for intravascular delivery and deployment.In a specific embodiment, the device could reside on the outer surfaceof a stent and be held in place between the outer stent wall and theinner vessel wall. Functionally, the receiver-stimulator devicecomprises 1) an ultrasound transducer to receive the acoustic energyfrom a controller-transmitter device and transform it into electricalenergy, 2) an electrical circuit to transform the alternating electricalenergy into a direct current or waveform having other characteristics,and 3) electrodes to transfer the electrical energy to the myocardium.The receiver-stimulator would use signal information from the acousticenergy transmission to configure the electrical output, for example thepulse width of the transmission would determine the pulse duration/widthof the electrical output waveform. Additionally, the receiver-stimulatormay comprise circuitry for additional control logic, for exampleselecting activation of individual receiver-stimulators (on-offcontrol), timing delays, waveform shape adjustments, or the like. Inparticular, when more than one receiver-stimulator is implanted to becontrolled by a single controller-transmitter, the transmitted energysignal may contain addressing or selection information identifying whichreceiver-stimulator is to be activated at any particular time.

Subsequently, a controller-transmitter device would be implantedsubcutaneously utilizing known surgical techniques (above or beneath thepectoral muscles) near the heart; this device containing some or most orall elements of currently available pacemaker systems, with specificadaptations pertinent to this invention. Such typical pacemaker elementsmay include a power source, pacemaker control and timing circuitry, asensing system possibly comprised of ECG sensing electrodes, motiondetectors, body or other temperature sensors, pressure sensors,impedance sensors (e.g., for measuring respiration cycles or lungedema), or other types of physiologic sensors, signal conditioning andanalysis functions for the various electrodes and detectors, and asystem to communicate with an outside console for data transmission,diagnostic, and programming functions typically through a radiofrequency(RF) link. Additionally, the controller-transmitter device would containan ultrasound amplifier and an ultrasound transducer to generateacoustic energy, and transmit such energy in the general direction ofthe heart and specifically in the direction of the implantedreceiver-stimulator device. The duration, timing, and power of theacoustic energy transmission would be controlled as required, inresponse to detected natural or induced physiological events orconditions, and per known electrophysiological parameters, by thepacemaker control electronics.

A single receiver-stimulator device may be implanted as described abovefor single site pacing; additionally it would be possible to implant aplurality of receiver-stimulator devices which would stimulate eithersimultaneously by receiving the same transmitted acoustic energy, orsequentially through fixed or programmable delays after receiving thesame transmitted acoustic energy, or independently by responding only tosignal information of the transmitted acoustic energy of a specificcharacter (i.e., of a certain frequency, amplitude, or by othermodulation or encoding of the acoustic waveform) intended to energizeonly that specific device.

In a first preferred embodiment a leadless cardiac pacemaker would beemployed as a left ventricular pacemaker functioning as a “slave”pacemaker to an implanted conventional (i.e., utilizingleads/electrodes) right heart pacemaker, either a single or preferably adual chamber type. The purpose of such a slave system would be toprovide left ventricular pacing synchronous with the right ventricularpacing provided by the right heart pacemaker as an advantageoustreatment for patients with HF, but without necessitating the placementof a left ventricular lead.

In such an embodiment the receiver-stimulator would be implanted at adesired location within the left ventricle, preferably fully embeddedwithin the myocardium. A specialized controller-transmitter would thenbe implanted subcutaneously at a location allowing insonification of theimplanted receiver-stimulator. The specialized “slave”controller-transmitter would include sensing electrodes on orincorporated into its external surface and signal processing circuitryand algorithms to allow it to detect pacing artifact signals from animplanted conventional right heart pacemaker and/or the patient'selectrogram (electrocardiographic recording). Signal processing andspecialized algorithms would differentiate pacing artifact signals,native cardiac electrogram signals occurring from intrinsic atrialand/or ventricular activation, and/or native cardiac electrogram signalsoccurring from non-intrinsic atrial and/or ventricular activationinitiated from pacing. The slave controller-transmitter would thenrespond to the right atrial or right ventricular or both pacing artifactsignals from the right heart pacemaker, or would respond to detectedintrinsic or non-intrinsic activation, and transmit acoustic energy tothe implanted receiver-stimulator in order to produce a left ventricularstimulation at the desired time in relation to the right atrial and/orright ventricular paced artifact or detected/sensed cardiac event. Forexample, when transmission occurs immediately upon the detection of aright ventricular pacing artifact, a left ventricular pacing stimulus isdelivered by the receiver-stimulator pacing output in the left ventricleto produce bi-ventricular pacing therapy.

Alternately, the implanted controller-transmitter could be adapted towork in conjunction with a conventional bi-ventricular pacemakertypically having three leads for the right atrium, right ventricle, andleft ventricle. In one adaptation, in order to eliminate the requirementto place the left ventricular lead, the controller-transmitter wouldconnect via a special wire to the conventional pacemaker's leftventricular output. The controller-transmitter would then detect theconventional pacemaker's left ventricular pacing output from the specialwire and immediately transmit acoustic energy to activate thereceiver-stimulator implanted into the left ventricle. Such a systemwould offer elimination of the left ventricular lead and require only asimple controller-transmitter unburdened by sensing electrodes andassociated signal processing circuitry and algorithms. In anotheradaptation, the input for the left ventricular lead in the conventionalbi-ventricular pacemaker header could be sealed off, and the specialized“slave” controller-transmitter would operate as described in theparagraph above.

Another preferred embodiment is a leadless stand alone single chamberpacemaker. Such an embodiment would utilize the same or a similarimplantable receiver-stimulator device as described above, however inthis case it would be implanted into or attached to the right atrium ofthe heart in order to provide right atrial pacing, or implanted into orattached to either the right ventricle or left ventricle of the heart inorder to provide right or left ventricular pacing. Thecontroller-transmitter would then incorporate most or all of thefeatures of a contemporary single chamber pacemaker device, typicallyknown as an AAI (atrial) or VVI (ventricular) mode pacing. Suchconventional pacemakers commonly utilize right atrial or rightventricular leads for treatment of bradyarrhythmias, or slow heart rate.A pacemaker system per this invention would advantageously not requirethe use of electrical leads of any kind. Moreover, the ability to use aleft ventricular lead alone enables the potential hemodynamic benefit ofleft ventricular pacing compared to a right ventricular pacing withoutthe use of electrical leads of any kind. Further enhancement to thissingle chamber pacemaker system would include other patientphysiological sensor(s) that adjust the patient's paced rate in responseto the sensor, e.g., motion detectors. This would provide the capabilityfor AAIR and VVIR modes of pacing.

As described previously, sensing of electrical activity in the body andother patient physiological information such as movement, bloodpressure, intracavity impedance changes, or heart sounds would beprovided from electrodes and/or other sensors incorporated onto or intoor within the housing of the implanted controller-transmitter. In aparticular adaptation the transmitting transducer for thecontroller-transmitter may be used as a sensor for mechanical/motionsensing or for heart sound sensing. Examples for electrical activitysensing include intrinsic cardiac beats, pacemaker pacing artifacts,non-intrinsic cardiac beats initiated by pacemaker pacing outputs, andthe like.

In another preferred embodiment of the leadless cardiac pacemaker systema dual chamber pacemaker could be constructed, with function similar topresent dual chamber (DDD) pacemakers. Such a pacemaker would berealized by utilizing two implantable receiver-stimulator devices andeither one or two implantable controller-transmitter devices. Onereceiver-stimulator device would be implanted into or attached to theright atrium as described above, the second would be implanted into orattached to the right or left ventricle. One implantedcontroller-transmitter device would transmit ultrasound to the twoimplanted receiver-stimulators, causing the receiver-stimulators toprovide pacing stimulation to the atrium and ventricle eithersimultaneously or sequentially. If sequential, timed stimulation to theatrium and ventricle is required, various means to accomplish this couldbe incorporated into the leadless pacemaker system. In one possibility,a single acoustic waveform would be transmitted at the time necessary toactivate the first, typically atrial, receiver-stimulator. The second,typically ventricular, receiver stimulator device would be of a modifieddesign incorporating circuitry and devices to capture and temporarilystore the acoustic energy transmitted at the time of atrial stimulation,and after a fixed delay provide this energy to its stimulationelectrodes to pace the ventricle. Sequential stimulation could also beaccomplished under direct control of the controller-transmitter,possibly utilizing the sequential transmission of acoustic energy atdifferent frequencies, with each receiver-stimulator tuned to respondonly to a single unique frequency. Other methods including amplitudemodulation, frequency modulation, time-division modulation, or othermodulation or encoding of the acoustic waveform would also permitselective and sequential pacing from multiple implantedreceiver-stimulator devices. Alternately, two controller-transmitterscould be implanted, each configured to transmit acoustic energy only toone specific receiver-stimulator, such configuration achieved eitherthrough spatial separation, frequency separation, or other modulation orencoding means as previously described.

In such a dual chamber system, sensing of the electrogram or otherpatient physiological information would be provided from electrodesand/or other sensors incorporated onto or into or within the housing ofthe implanted controller-transmitter. Further enhancement to this dualchamber pacemaker system would include other patient physiologicalsensor(s) that adjust the patient's paced rate in response to thesensor, e.g., motion detectors. This would provide the capability forDDDR modes of pacing.

It can be seen that a dual chamber pacemaker system as described abovecould be further adapted as a bi-ventricular pacemaker for HFapplications. In one embodiment of a bi-ventricular pacemaker the systemdescribed above, with appropriate adaptations to the timingconsiderations between the two pacing signals, could be employed withone receiver-stimulator implanted into the right ventricle and thesecond receiver-stimulator implanted into the left ventricle. In afurther enhancement a third receiver-stimulator could be implanted intothe right atrium to provide both dual chamber right-sided pacing withsynchronous left ventricular pacing. As described above, means toprovide proper sequencing of the multiple pacing stimuli would beemployed.

In another preferred embodiment, the leadless cardiac pacemaker systemcould be used in conjunction with a conventional single chamber or dualchamber implantable cardioverter-defibrillator (ICD) device. The ICDdevice utilizes a conventional lead/electrode system for (optionally)right atrial and right ventricular sensing and pacing, withdefibrillation electrodes combined onto the right ventricular lead. Aleadless receiver-stimulator device per this invention could beimplanted into the left ventricle, with the combined deviceincorporating left ventricular pacing, similar to current lead-basedCRT-D (integrated ICD and cardiac resynchronization pacing) devices. Areceiver-stimulator implanted into the left ventricle would receiveacoustic energy from a specialized controller-transmitter to providestimulus to the left ventricle. The specialized controller-transmitterwould be implanted subcutaneously at a location allowing insonificationof the implanted receiver-stimulator. Such a system would beadvantageous with respect to conventional CRT-Dpacemaker/defibrillators, again by eliminating the requirement for theleft ventricular lead and the problems associated with its placement.

In another preferred embodiment, the leadless cardiac pacemaker systemcould be combined with a conventional pacemaker system in a singledevice. Preferably, such a dual chamber (DDD) pacemaker would utilize aconventional lead/electrode system for right atrial and ventricularsensing and pacing connected to the header of the pulse generator case.The DDD pulse generator case would also contain an acoustic transmitter.In addition to the right atrial and right ventricular pacingaccomplished through the conventional leads, a leadlessreceiver-stimulator device per this invention could be implanted intothe left ventricle. The implanted receiver-stimulator would receiveacoustic energy from the transmitter incorporated into the otherwiseconventional pacemaker to provide stimulus to the left ventricle. Such asystem would be advantageous with respect to conventional bi-ventricularpacemakers by eliminating the requirement for the left ventricular leadand the problems associated with the placement thereof.

In still another preferred embodiment, the leadless cardiac pacemakersystem could be combined with conventional implantablecardioverter-defibrillator (ICD) technology in a single device.Preferably, such a device would utilize a conventional lead/electrodesystem for right atrial and ventricular sensing and pacing anddefibrillation connected to the header of the pulse generator case. TheICD pulse generator case would also contain an acoustic transmitter. Inaddition to the right atrial and ventricular pacing and defibrillationaccomplished through the conventional leads, a leadlessreceiver-stimulator device per this invention could be implanted intothe left ventricle, with the combined device incorporatingbi-ventricular pacing, similar to current lead-based (CRT-D) devices. Areceiver-stimulator implanted into the left ventricle would receiveacoustic energy from the transmitter incorporated into the otherwiseconventional ICD device to provide stimulus to the left ventricle. Sucha system would be advantageous with respect to conventional CRT-Dpacemaker/defibrillators, again by eliminating the requirement for theleft ventricular lead and the problems associated with its placement.

Patients requiring ICD devices have potentially lethal heart rhythmsincluding ventricular tachycardia and fibrillation. Having theadditional capability to select the location for a left ventricular leadplacement for terminating episodes of ventricular tachycardia usingantitachycardia pacing techniques should be more effective compared tocurrent devices. The advantage of terminating tachycardia withselected-site left ventricular pacing may be the avoidance of painfulhigh energy shocks. Moreover, the capability of implanting multiplereceiver-stimulators in any heart chamber may allow multisite pacing forthe prevention or termination of atrial fibrillation and ventricularfibrillation.

The methods and systems of the present invention may be utilized forantitachycardia pacing (ATP), including prevention algorithms, utilizingacoustic energy to transmit energy and signal information from anacoustic controller-transmitter, which may optionally be implanted orexternally located, to one or more implanted receiver-stimulators havingelectrodes adapted to be implanted in direct contact with cardiactissue. The acoustic controller-transmitter will usually have ECG orother monitoring means that allow detection of tachycardia, permittingtiered treatment via pacing and optionally higher energy defibrillationand/or cardioversion. In all cases, the energy will be delivered and/orcontrolled by acoustic signals from the controller-transmitter to theacoustic receiver-stimulator(s). The acoustic receiver-stimulators willconvert the acoustic energy intostimulating/pacing/defibrillation/cardioversion electrical energy.

Such a leadless pacing system may advantageously be employed as a standalone antitachycardia pacemaker. In this embodiment of the presentinvention, one or more of the receiver-stimulators would be implanted atone or more cardiac sites, and the controller-transmitter may be eithera subcutaneously implanted device or an externally applied device.

The leadless pacing system could also be employed along with animplanted conventional (i.e., utilizing leads/electrodes) right heartpacemaker, or along with an implanted conventional right heartpacemaker/cardioverter/defibrillator, either a single or preferably adual chamber type. The purpose of such a combination of systems would beto provide site-specific pacing for termination or prevention oftachyarrhythmias. Alternatively, the leadless pacing system implanted incombination with a pacemaker/cardioverter/defibrillator provides thepatient with a high energy shock capability in case the pacing therapyis ineffective in termination of the arrhythmia.

In a further embodiment a leadless cardiac pacemaker system would beemployed along with an implanted subcutaneous, leadlesscardioverter/defibrillator. The purpose of such a combination of systemswould be to provide a leadless pacing capability for antitachycardiapacing therapy, for backup pacing post shock delivery, and/or forbradycardia pacing support. The implanted subcutaneous, leadlesscardioverter/defibrillator provides the patient with a high energy shockcapability in case the pacing therapy is ineffective in termination ofthe arrhythmia or accelerates the tachycardia to fibrillation.

In still further embodiments, a leadless cardiac pacemaker/defibrillatorsystem would be employed as a single integrated high energy electricalshock defibrillator and a leadless site-specific pacing system. Thepurpose of this integration would be to provide a single subcutaneouslyimplanted controller device.

Similarly, the controller-transmitter can be adapted to be usedconcomitantly with a leadless, subcutaneous defibrillator to provide thepacing capability. This can be done either as a standaloneantitachycardia pacing system, as a defibrillator-pacing system wherecommunication exchanges by a direct connection between the defibrillatorand the controller-transmitter, or as a single integrated device systemwith the capability for acoustic transmission to a receiver-stimulatorfor pacing (bradycardia backup or for antitachycardia pacing therapy)and for electrical shock for defibrillation.

In further aspects of the present invention, the controller-transmitterdevice may be implanted at a remote tissue location within or externalto the body. The receiver-stimulator device may be either permanentlyimplanted or temporarily placed at a target location with stimulatingelectrodes in direct contact with the body tissue to be stimulated. Byobserving changes in a patient response and/or device measurement inresponse to different combinations of remote and target tissuelocations, the sites chosen for permanent implantation may be optimizedand selected. Patient response(s) may be any quantitative or qualitativephysiologic responses to the stimulation, typically being associatedwith the desired beneficial response. Device measurement(s) could besignal strength, transmission efficiency, or the like.

Uses for such optimized placement methods include, but are not limitedto, applying electrical stimulation for the treatment of peripheralmuscle strains and tears, bone fractures, musculoskeletal inflammation,chronic pain, Parkinson's disease, epileptic seizures, high bloodpressure, cardiac arrhythmias, heart failure, coma, stroke, hearingloss, dementia, depression, migraine headaches, sleep disorders, gastricmotility disorders, urinary disorders, obesity, and diabetes.

The present application describes methods and systems to evaluateeffectiveness and optimize the positioning of these implantable leadlesssystems. Both the controller-transmitter and the receiver-stimulatorplacements are optimized with these methods. Three methods are describedusing testing sequences prior to permanent implantation that involveplacement of the devices in various locations of the body. In eachmethod, for a set of device locations, a patient response or a devicemeasurement is made. The optimum location is determined based upon thepatient responses and/or the device measurements.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 a and 1 b illustrate acoustic cardiac pacing, defibrillation,and cardioversion systems constructed in accordance with the principlesof the present invention.

FIGS. 2 a and 2 b illustrate different combinations of stand aloneacoustic cardiac pacemakers constructed in accordance with theprinciples of the present invention.

FIGS. 3 a and 3 b are block diagrams showing the components of theacoustic controller-transmitter and acoustic receiver-stimulators of thepresent invention.

FIG. 4 illustrates representative acoustic and electrical signals usefulin the systems and methods of the present invention.

FIGS. 5 a-5 c illustrate two embodiments of a small implantablereceiver-stimulator according to the principles of the presentinvention.

FIG. 6 is a block diagram illustrating methods for treatingtachyarrhythmia according to the principles of the present invention.

FIGS. 7 a-7 c illustrate systems according to the present invention fortreating tachycardias alone or in combination with pacing anddefibrillator systems.

FIG. 8 illustrates a stand alone acoustic cardiac pacemaker systemconstructed in accordance with the principles of the present invention.

FIGS. 9 a and 9 b illustrate an implanted cardiac pacemaker system inaccordance with the principles of the present invention.

FIGS. 10 a, 10 b, and 10 c illustrate a system useful for optimizingimplantation of the system of FIGS. 9 a and 9 b in accordance with theprinciples of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The systems and devices described comprise a controller-transmitterdevice that will deliver acoustic energy and information to one or moreimplanted receiver-stimulator device(s) that will convert the acousticenergy to electrical energy of a form that can be used to electricallypace the heart. The acoustic energy can be applied with ultrasound as asingle burst or as multiple bursts with appropriate selection of thefollowing parameters:

Parameter Value Range Ultrasound frequency 20 kHz-10 MHz Burst Length(#cycles) 2-10,000 Stimulation Pulse Duration 0.1 μS-10 mS Duty Cycle0.01-0.2% Mechanical Index ≦1.9

The controller-transmitter device would contain an ultrasound transduceror transducers of appropriate size(s) and aperture(s) to generatesufficient acoustic power and signal information to achieve the desiredstimulation at the location of an implanted receiver-stimulator device.Additionally, multiple implanted receiver-stimulator devices may beplaced within the region insonified by the controller-transmitterdevice. Multiple receiver-stimulator implants may functionsimultaneously, however it is possible for multiple devices to functionindependently, either by responding only to a specific transmittedfrequency, or through the use of a selective modulation technique suchas amplitude modulation, frequency modulation, pulse width modulation,or through encoding techniques including time-division multiplexing.Such a pacemaker system comprising a controller-transmitter and at leastone receiver-stimulator would preferably operate at an ultrasoundfrequency between 20 kHz and 10 MHz, and more preferably operate at afrequency between 100 kHz and 1 MHz, and most preferably operate at afrequency between 200 kHz and 500 kHz.

The signal information generated by the controller-transmitter will mostoften comprise pulse width and pulse amplitude information used by thereceiver-stimulator to construct a corresponding electrical output.Alternatively, the signal information may comprise address information(identifying a particular receiver-stimulator device or group of devicesto trigger), triggering information to initiate output (turn on or off)the receiver-stimulator device(s), delay information to control when thereceiver-stimulator device(s) initiate output, the level or othercharacteristics of the electrical power to be delivered, and the like.The receiver-stimulator device(s) will usually have circuitry to permitdecoding of the signal information (which will usually be encoded in thepower transmission), and additional circuitry such as a digital gatewhich can turn on and off the electrical output, timer circuitry topermit a delay in turning on or off the electrical output, and the like.

The controller-transmitter device containing the transmitting transducerwould be implanted typically just beneath the skin in the subcutaneousspace but could also be placed beneath the pectoral muscles.

The controller-transmitter device would typically include sensors suchas electrodes for detecting the patient's electrogram and/or pacingsignals (pacing artifacts) from other devices, and in certainembodiments additional physiological sensors including but not limitedto sensors which would detect the patient's motion, blood pressure,temperature, respiration, and/or heart sounds. Circuitry and algorithmsfor utilizing these signals for control of the pacemaker function wouldbe provided. Such electrodes and other sensors would be preferablydisposed on or incorporated into or within the housing of thecontroller-transmitter device.

The acoustic transmitter function may also be incorporated within adevice providing conventional lead-based electrical stimulation, forexample in a bi-ventricular pacemaker (CRT) or defibrillator (CRT-D)system wherein a conventional lead/electrode system would providesensing from and stimulus to the right atrium and ventricle, and thereceiver-stimulator would provide synchronized stimulation to the leftventricle.

Examples of leadless cardiac pacemaker systems are illustrated in FIGS.1 through 5 and 8 through 10.

FIG. 1 a illustrates a “slave” configuration for biventricular pacing inconjunction with a conventional implanted dual chamber pacemaker. Inthis example a controller-transmitter device 1 containing circuitry toprovide pacing control and ultrasound transmission, plus means tocommunicate with an outside programmer 3 is implanted beneath the skin,and generally over the heart. An ultrasound signal is transmitted bythis device through intervening tissue to the receiver-stimulator device2, shown implanted in the left ventricle, containing means to receivethis acoustic energy and convert it into an electrical pulse which maythen be applied to the attached electrodes. In this example aconventional dual chamber (DDD) pacemaker 5 utilizing both aconventional right atrial lead 6 and conventional right ventricular lead7 is also shown implanted. Controller-transmitter 1 incorporates sensingelectrodes 4 and appropriate circuitry and algorithms (not shown) thatallow detection of the patient's electrogram and/or the detection ofpacing signal artifacts generated by conventional pacemaker 5, providinginformation whereby the control circuitry can at the proper timeinitiate the acoustic transmission which will result in left ventricularpacing.

FIG. 1 b is a cross-sectional view of the heart in the previous example,showing a single receiver-stimulator device 2 implanted into the leftventricular myocardium, receiving acoustic energy fromcontroller-transmitter 1. Conventional leads 6 and 7 from pacemaker 5(not shown) are placed in the right atrium and right ventricle,respectively. Optionally (not shown), the receiver-stimulator device 2could be incorporated into a vascular stent deployed into a coronaryvein or artery on the epicardial surface of the left ventricle.

FIG. 2 depicts various combinations of stand alone leadless cardiacpacemakers. FIG. 2 a is a cross-sectional view of the heart showing asingle receiver-stimulator 2 implanted into the right ventricle,receiving acoustic energy from controller-transmitter 1. Such anembodiment matches the function of a single chamber (VVI) typepacemaker. Receiver-stimulator 2 could also be implanted into the leftventricle (not shown) to function as a VVI pacemaker. In anotheradaptation of this example (not shown), a single receiver-stimulatorcould be implanted into the right atrium to create a single chamber(AAI) type of pacemaker.

FIG. 2 b shows a further adaptation wherein two receiver-stimulatordevices 2 are implanted to achieve a leadless bi-ventricular pacemakerconfiguration. The first receiver-stimulator 2 is shown attached to theright ventricular apex with the second being attached to the leftventricular free wall. Both receiver-stimulator devices 2 receiveacoustic energy from controller-transmitter 1, either simultaneously orselectively through methods that may include amplitude modulation,frequency modulation, time-division modulation, or other modulation orencoding of the acoustic waveform. In another adaptation (not shown) oneof the receiver-stimulator devices could be implanted within the rightatrium rather than the left or right ventricle to result in a dualchamber (DDD) type of pacemaker. In a further adaptation (not shown),three receiver stimulator devices could be implanted, into the rightatrium, right ventricle, and left ventricle and activated eithersimultaneously or sequentially through the previously described methods.

A leadless cardiac pacemaker system is shown in more detail in the blockdiagram of FIGS. 3 a and 3 b. In FIG. 3 a the controller-transmitterdevice 1 is comprised of: a battery 10 which is optionally arechargeable battery; multiple electrodes and possibly other sensorsincluding motion sensors 11 which may be in direct contact with tissueto detect the patient's electrocardiogram, pacing signals from otherconventional pacemakers, and other physiological parameters possiblyincluding patient activity; these being connected to signal processingcircuitry 12; a communications module 13 whose function is to provide adata path, for example by RF communication, to and from an external unit3 to allow the physician to set device parameters and to acquirediagnostic information about the patient and/or the device; a controland timing module 14 which stores such setup parameter and diagnosticinformation and uses this information in conjunction with the acquiredphysiological data to generate the required control signals for theultrasound amplifier 15 which in turn applies electrical energy to theultrasound transducer 16 which in turn produces the desired acousticbeam. The controller-transmitter device 1 is encased in a hermeticallysealed case 17 constructed of a biologically compatible material,typical of currently existing pacemaker or ICD devices.

Referring to FIG. 3 b, the receiver-stimulator device 2, implanted inthe path of the acoustic beam at the location where electricalstimulation is desired, contains an ultrasound transducer 20 whichintercepts a portion of the transmitted acoustic energy and converts itinto an alternating electrical signal representing the alternatingnature of the applied ultrasound pressure wave. This electrical signalis applied to an electrical circuit 21 which may be one of a typecommonly known as an envelope detector, and which may have one of manyknown circuit configurations, producing a voltage pulse with amplitudeproportional to the amplitude of the transmitted ultrasound burst andwith a pulse length generally equal to the length of the transmittedburst. The circuit 21 may also be of different configurations andfunction, for example to provide a fixed delay between the reception ofthe acoustic energy and the output of the pacing pulse, or to provideoutput signals having characteristics other than a single pulse. Thissignal is applied then to electrodes 22 which may be incorporated ontothe outer surface of the device, and thus in direct contact with thetissue which is to be stimulated. The receiver-stimulator device 2 isalso enclosed within a hermetically sealed case 23 of biologicallycompatible material.

Referring also to previously described FIGS. 3 a and 3 b, FIG. 4provides detail representing example acoustic and electrical signals ofthe present system. FIG. 4 first depicts a train of pacing pulses 31which have the desired width and are repeated at a desired interval. Thecontroller-transmitter device 1 produces one or multiple acoustictransmissions 32, at the desired pacing pulse width and repeated at thedesired pacing pulse interval, which are emitted from the ultrasoundtransducer 16. Below waveform 32 is shown an enlargement 33 of a singleacoustic burst. This burst again has a desired width, a desiredoscillation frequency F=1/t, and also a desired acoustic pressureindicated by the peak positive pressure P+ and peak negative pressureP−. The acoustic pressure wave, when striking the receiving transducer20 of the receiver-stimulator device 2 generates an electrical signal 34having frequency and burst length matching that of the transmittedwaveform 33 and amplitude proportional to the transmitted acousticpressure P+/P−). This electrical waveform is then rectified and filteredby the circuit 21 producing the desired pulse 35 with length equal tothe burst length of the transmitted waveform 33 and amplitude(V_(PULSE)) proportional to the amplitude of the electrical signal 34.Thus, it can be seen in this example that it is possible to vary thepacing rate by varying the time between ultrasound bursts, to vary theduration of any one pacing pulse by varying the duration of theultrasound burst, and to vary the amplitude of the pacing pulse byvarying the amplitude of the ultrasound waveform.

In practice, the amount of energy (amplitude) received by the implantedreceiver-stimulator device will vary due to ultrasound attenuationcaused by loss in the intervening tissue and bone, due to spatiallocation of the receiver-stimulator device with respect to thetransmitted ultrasound beam as such a beam is typically non-uniform fromedge-to-edge, and possibly due to orientation (rotation) of thereceiver-stimulator device with respect to the controller-transmitterdevice. Such variation would affect the amplitude of the stimulationoutput pulse for any given ultrasound transmit power (acoustic pressureamplitude). This limitation can be overcome by adjusting the ultrasoundtransmit power until stimulation is consistent, a technique similar tothat used currently to determine pacing thresholds at the time ofpacemaker implantation; additionally this can be adjusted automaticallyby algorithms within the controller-transmitter device that periodicallydetermine stimulation thresholds and adjust power transmissionaccordingly to compensate for any change in the system includingrelative movement between the transmitting and receiving devices. Thislimitation may also be mitigated by design of the transducerincorporated into the receiver-stimulator device to be omni-directionalin its reception capability, for example by using a spherical transduceror by using multiple transducers disposed at appropriate angles toreduce or eliminate the directional sensitivity of the device.

FIGS. 5 a through 5 c illustrate two embodiments of a small implantablereceiver-stimulator of a cylindrical profile, suitable for placement bycatheter, stylet, or other means adapted for its delivery. FIG. 5 ashows in plan view and 5 b in perspective view such areceiver-stimulator 2 having a hollow, cylindrical ultrasound transducer51, a circuit assembly 52 comprising at least a detector circuit andpossibly other circuits and functions, and two electrodes 53 at eitherend of the assembly. The transducer 51 would be of a rigid piezoelectricmaterial, typically a piezoelectric ceramic or single crystalpiezoelectric element with electrodes deposited on the opposing surfacesof the cylinder. Alternately (not shown), the transducer 51 could befabricated from multiple smaller cylindrical sections connected eitherin series, in parallel, or a combination thereof. Alternately (notshown), the transducer 51 might be a composite fabrication containingmultiple elements disposed about the cylindrical body. The transducerand circuit would be enclosed in an electrically insulating butacoustically transparent biocompatible housing 54. The circuit assembly52 may be fabricated using known surface-mount or hybrid assemblytechniques, upon either a fiberglass or ceramic substrate. Electrodes 53would be fabricated of material commonly used in implanted electrodes,such as platinum, platinum-iridium, or preferably of a steroid-elutingdesign. Necessary electrical wiring between the transducer, circuitboard, and electrodes is not shown in these drawings. Thereceiver-stimulator of this design would also incorporate means such ashelical coils, barbs, tines, clips, and the like (not shown) to affixthe device within, or onto, or in contact with, the myocardium in thedesired location. Such fixation means may vary depending on the intendedimplant location and delivery method. Typical dimensions of such adevice would be 1.5 cm in length and 3.0 mm in diameter, and preferablyless than 1.0 cm in length and 2.0 mm in diameter, exclusive of fixationfeatures.

As shown in FIG. 5 c, by using hybrid circuit techniques it may bepossible to further miniaturize the circuit assembly 52 such that itwould fit inside the hollow interior of the transducer 51. This wouldhave the benefit of substantially reducing the length of the finisheddevice.

As depicted in FIG. 8, for the treatment of tachycardias, one or morereceiver-stimulator elements 2 would be implanted within the heart. Inthis illustration receiver-stimulators are implanted in the leftventricle. For ATP, the device(s) would be implanted at sites whichwould be optimal for interacting with a tachycardia episode. Using VT asan example, standard electrical activation sequence mapping performedduring VT can identify the location and pathway of the VT reentrycircuit within the left ventricle as well as areas of slow conduction.Using this testing, a specific site or sites can be identified thatwould be most responsive to ATP algorithms. A single receiver-stimulatormay be sufficient to treat the rhythm disorder however using multiplereceiver-stimulators increases the ability to pace at different sitesand perhaps at different times to effectively block the conduction ofthe arrhythmia in order to terminate the condition. The use of multiplereceiver-stimulators would generally be used for the suppression ortreatment of atrial fibrillation and ventricular fibrillation. Thecontroller-transmitter 1 would be implanted in a subcutaneous locationand situated to insonify the receiver-stimulators. Pacing sequenceswould originate in the controller-transmitter based on ATP algorithmsintended to terminate the tachycardia. The controller-transmitter maycontain one or more algorithms that deliver pacing therapy in attemptsto terminate the arrhythmia. In its simplest embodiment, no othercomponents illustrated in FIG. 8 are necessary for treating tachycardia.

The leadless cardiac pacemaker system shown in FIGS. 3 a and 3 b may beadapted for treating tachycardias as follows. The controller-transmitterdevice 1 is comprised of a battery 10 which is optionally a rechargeablebattery; multiple electrodes and/or other sensors 11 which may be indirect contact with tissue to detect the patient's electrocardiogram,pacing signals from other conventional pacemakers, and/or otherphysiological parameters possibly including patient activity; thesebeing connected to signal conditioning/processing circuitry 12; acommunications module 13 whose function is to provide a data path, forexample by RF communication, to and from an external programming and/orcommunicating unit 3 to allow the physician to set device parameters andto acquire diagnostic information about the patient and/or the device;an arrhythmia detection, control, and timing module 14 which processeselectrogram or other cardiac information to determine the presence orabsence of a tachycardia, stores setup parameters, stores diagnosticinformation and uses this information in conjunction with the acquiredphysiological data to generate the required control signals for theultrasound amplifier 15 which in turn applies electrical energy to theultrasound transducer 16 which in turn produces the desired acousticbeam. By varying the timing and control of the output, antitachycardiaprevention and termination pacing algorithms are delivered from thecontroller-transmitter. The controller-transmitter device 1 ispreferably encased in a hermetically sealed case 17 constructed of abiologically compatible material, typical of currently existingpacemaker or ICD devices.

A simple block diagram of logic used for arrhythmia detection andantitachycardia pacing therapy control is depicted in FIG. 6. Thearrhythmia detection algorithm 118 would use known techniques and dataprocessed from the electrogram or other cardiac information, forexample, rate determination, rate variability, waveform morphology,time/signal excursions from baseline etc., to determine whether atachycardia episode is present. The therapy delivery algorithm 119 woulduse known techniques for therapy algorithms for example burst pacing,rate adaptive pacing, overdrive suppression pacing, autodecrementalpacing, premature stimuli, etc. to terminate the arrhythmia. One or moredetection schemes or pacing therapies may be present in the controller14 and adjusted based on programming communication to the controller 14.

Examples of leadless cardiac pacemaker systems suitable for delivery ofATP are illustrated in FIG. 1 a with systems specifically adapted forATP and illustrated in FIGS. 7 a to 7 c and 8.

FIG. 1 a illustrates a “slave” configuration for leadless ATP used inconjunction with a lead-based pacemaker, cardioverter, and/ordefibrillator device. Similar to the previous description for FIG. 1 a,the controller-transmitter would detect pacing signals generated by theco-implanted pacemaker or defibrillator and initiate an acoustictransmission to activate the receiver-stimulator with each ventricularpacing signal detected. The algorithm logic for the detection of thearrhythmia and the delivery of ATP would be a component of the pacemakeror defibrillator.

FIG. 7 a illustrates a leadless ATP device used in conjunction with aleadless cardioverter or defibrillator device. FIG. 7 b illustrates anintegrated leadless device using acoustic transmission toreceiver-stimulators for ATP and using high energy subcutaneouselectrodes for cardioversion and/or defibrillation. FIG. 7 c illustratesan integrated lead-based defibrillator device incorporating a leadlesspacing system that uses acoustic transmission to receiver-stimulatorsfor ATP and uses a high energy coil electrode on a lead in the RV forcardioversion and/or defibrillation. FIG. 8 represents the a stand aloneconfiguration for an ATP device as described above.

In FIGS. 9 a and 9 b, an implanted leadless single chamber cardiacpacemaker system of the present invention is illustrated in an exemplaryembodiment as a “standalone” cardiac pacemaker system. As can beappreciated this standalone system can be adapted to a dual chambersystem (not shown). FIG. 9 a, depicting the controller-transmitterdevice 61 containing circuitry to provide pacing control and acoustictransmission, is implanted just beneath the skin, and generally over theheart. The controller-transmitter includes wireless circuitry tocommunicate with an outside programmer 63. Acoustic energy istransmitted by controller-transmitter device 61 through interveningtissue to a receiver-stimulator device 62 containing transducers andcircuitry to receive the acoustic energy and convert it into electricalpulse(s) which may then be applied to tissue through the attachedelectrodes. In FIG. 9 b, receiver-stimulator device 62 is shown attachedto the left ventricular septum. The receiver-stimulator device 62 isshown as a small cylindrical or button-shaped device that would beaffixed to the heart muscle with an attaching screw-in helix, similar toconventional pacing lead wires fixed to the heart as in currentpacemaker systems, or other method (for example with barbs, tines,clips, sutures or the like) of attaching permanently implanted devicesto the heart.

FIGS. 10 a, 10 b, and 10 c, illustrate a testing and positioning systemfor a leadless cardiac pacemaker system as in any of the aboveembodiments, for example as depicted in FIGS. 9 and 9 b. The testing andpositioning system is used to evaluate various positions for implant ofthe receiver-stimulator 62 in the heart and for implant of thecontroller-transmitter 61 in the chest. Testing is performed forexample, to determine appropriate levels of transmitted and receivedacoustic energy and subsequent electrical output energy from thereceiver-stimulator required to capture/pace cardiac tissue. Knowledgeof the amplitude of transmitted energy would be needed to optimizepositioning of the implanted receiver-stimulator and implantedcontroller-transmitter, for example to efficiently utilize batterypower. Further, testing may be performed to identify areas on the chestthat would ensure acoustic reception by the receiver-stimulators withoutrestriction from chest contours or interference from the lungs or otherinternal tissue structures. This is referred to as an acoustic window ora targeting window. Still further, testing may be performed to assesspatient response, for example electrophysiologic or contractionresponses based on capture/pacing at a site. The observed patientresponse would be evidence of pacing on the electrocardiogram or othermeasures of heart function such as blood pressure or contractility.

An external controller-transmitter system 64 will generally be used forpositioning and testing, which will typically be able to be reused ondifferent patients. Controller-transmitter device 64 includes externalacoustic transmitter 65 and manual or other controller 66, typicallyconnected by cable 67, however it can be appreciated that thetransmitter 65 could be integrated into controller 66 and the integrateddevice used as an external transmitter. Transmitter 65 is typicallyplaced overlying the skin surface, with acoustic transmission gel usedfor coupling. Also used in the testing and positioning system, as shownin FIGS. 10 b and 10 c, is a receiver-stimulator device 62, which may bepositioned in any endocardial location using venous or arterialtransvascular access to the heart with a catheter-based delivery system68. Prior to permanent insertion (implant) of the receiver-stimulator 62into the tissue, device 62 will be temporarily mounted onto deliverysystem 68. Alternatively (not shown) a similar catheter-based devicecontaining a receiver-stimulator element that is permanently affixed onthe device may be used for site selection by positioning and testingsites anywhere on the endocardium or in the myocardium. FIG. 10 c showsfurther detail of a typical delivery system 68 for receiver-stimulatordevice 62. Ideally, prior to permanent insertion/deployment from thedelivery system, the pacing electrodes on the receiver-stimulator wouldaccessible via connecting wires that run the length of the deliverysystem (not shown). This example of a delivery system 68 comprises acatheter 69 onto which receiver-stimulator device 62 is affixed to thedistal end. Catheter 69 with receiver-stimulator 62 is inserted into asteerable guiding sheath 70. Other possible variations of deliverysystem 68 may be utilized, including a catheter 69 which is steerableand would be used in place of a steerable guiding sheath. Deliverysystem 68 enables manipulation and repositioning of receiver-stimulator62 within the vasculature or heart chambers. In this example, thedelivery system 68 would position the receiver-stimulator 62 and testthe cardiac site, then the delivery system 68 would be moved to anotherlocation and that site tested. Once an optimal position is found,implantable device 62 would be deployed from catheter 69, by first beingimplanted at the tested location by a fixation means and then beingreleased from catheter 69 by a mechanical means. In an alternative case,the testing catheter 69 with permanently affixed device 62 is removedfrom steerable guiding sheath 70, and a second catheter 69 having areleasable implantable device 62 is introduced to the location bycatheter 69 through steerable guiding sheath 70, or a separate deliverysystem 68 adapted to implant device 62.

A first method may be used in situations in which the ideal location forthe controller-transmitter 61 is known or limited due to anatomicconstraints, but more than one location for the receiver-stimulator 62is possible. Typically, the external controller-transmitter 64 will beused for testing purposes with acoustic transmitter 65 positioned on theskin surface overlying its ideal or otherwise predetermined location.Transmission gel will be used as coupling agent between the externalacoustic transmitter 65 and the skin. Alternatively, (shown in FIG. 9a), an implantable controller-transmitter device 61 may be surgicallyplaced under the skin in the final implant location and controlled withan external programmer. The receiver-stimulator device 62 will be placedin a first test position by maneuvering delivery system 68. Acousticenergy will then be transmitted/delivered using external controller 66or alternatively the implantable controller-transmitter 61 underdirection of programmer 63 to evaluate efficacy at that location. If theresults are not satisfactory or if there is a desire to evaluateadditional positions, the receiver-stimulator device 62 will be moved toa new site with the aid of delivery system 68, acoustic energy will betransmitted/delivered, and efficacy at this site will be tested. Thissequence can be repeated until the desired location for implantation ofthe receiver-stimulator device 62 is identified. The receiver-stimulatordevice 62 will then be delivered or deployed to that location and thedelivery system 68 removed. If an external controller-transmitter 64 wasused, but an implanted device 61 is intended to be implanted, thelocation of the externally applied controller-transmitter will be notedand an incision and dissection will be performed, as known in the art,for implantation of device 61.

One example (in addition to cardiac pacing) in which this method may beutilized is epilepsy, where the controller-transmitter location will beknown because it will be confined to a site near the craniotomy. In thiscase, a multiplicity of receiver-stimulators will typically be implantedinto the brain tissue. The controller-transmitter typically would bepositioned outside of the brain tissue either within the craniotomyopening or outside the cranium under the skin. The positioning andtesting of the placement of the receiver-stimulators will be based uponthe effects of the electrical stimulation on electroencephagraphymapping. Another example in which this method may be utilized isParkinson's disease, wherein, similar to the treatment of epilepsy, thecontroller-transmitter will be confined to a site near the craniotomyand a multiplicity of receiver-stimulators will typically be implantedinto brain tissue. In the case of Parkinson's disease, however, theplacement of the receiver-stimulators may be based upon the effects ofelectrical stimulation on patient responses such as reducing tremor.

A second method of optimization may be used in situations in which theimplant location for the receiver-stimulator is known, but the ideallocation for the controller-transmitter implant may vary. Thereceiver-stimulator device 62 is first implanted in its ideal locationor alternatively held in its ideal location by delivery system 68. Thetransmitter 65 of the external controller-transmitter device 64 isplaced at the first test location on the skin, using transmission gelfor coupling. Energy is then transmitted/delivered using externalcontroller 66 to evaluate efficacy at this location. The transmitter 65can be moved and the testing sequence repeated until the desiredposition is identified. The implantable controller-transmitter 61 isthen implanted at the location identified to be optimal.

One example in which this method may be utilized is in the treatment ofbone fractures. In this case, the location of the receiver-stimulatordevice will be determined by the location of the fracture. Possiblelocations for the controller-stimulator device can then be tested tooptimize transmission of acoustic energy.

A third method of optimization may be used in situations in which theimplant location for neither the receiver-stimulator device 62 nor thecontroller-transmitter device 61 is known. This method utilizesprocedures specified above in both the first and second methods. In thissituation, after testing the devices at initial locations, the locationsof both the devices are changed in alternation in subsequent testing,and this is repeated until the desired, optimal results are obtained.Then, both devices 61 and 62 are implanted.

One example in which this third method may be utilized is a cardiacpacemaker capable of multisite pacing (such as a dual chamber pacemakeror bi-ventricular pacing for heart failure). There are many potentiallocations to implant the receiver-stimulator devices, but some locationswill provide better physiological benefit to the patient. The ideallocation for the controller-transmitter device will be the site wherethe most acoustic energy can be delivered to the multiplereceiver-stimulator devices, but there may be some constraints onlocation imposed by the chest contour and the intervening lungs.Therefore, optimization of the implant locations for the devices mayrequire testing at different sites for each device. The observed patientresponse would be evidence of pacing on the electrocardiogram or othermeasures of heart function such as blood pressure or contractility.

These methods can be beneficial to all the applications of theimplantable leadless stimulator system and are not meant to be limitedto the examples provided herein.

1. A method for selecting and optimizing the implant locations of acontroller-transmitter device and a receiver-stimulator device, saidmethod comprising: positioning a controller-transmitter at a remotetissue location; positioning a receiver-stimulator at a target tissuelocation; activating the controller-transmitter to deliver acousticenergy to the receiver-stimulator so that said receiver-stimulatordelivers electrical energy into the target tissue location; observing afirst response; repositioning at least one of the controller-transmitterand the receiver-stimulator; observing a subsequent response; comparingthe first and subsequent response(s) and determining whichcontroller-transmitter and/or receiver-stimulator positions(s) is/arebetter; selecting position(s) that is/are better; and implanting acontroller-transmitter device and a receiver-stimulator device atrespective selected positions.
 2. A method as in claim 1, wherein thecontroller-transmitter used for positioning is an externally applieddevice used to select the site for an implantable controller-transmitterdevice.
 3. A method as in claim 1, wherein the receiver-stimulator usedfor positioning is a temporarily applied device used to select the sitefor an implantable receiver-stimulator device.
 4. A method as in claim1, wherein the response is a patient response.
 5. A method as in claim4, wherein the target tissue location is cardiac tissue, the remotetissue location is on the chest over the heart, and the observed patientresponse is heart function.
 6. A method as in claim 4, wherein thetarget tissue location is cardiac tissue, the remote tissue location ison the chest over the heart, and the observed patient response iselectrocardiographic.
 7. A method as in claim 1, wherein the response isa device measurement.
 8. A method as in claim 7, wherein the devicemeasurement is the electrical output amplitude of thereceiver-stimulator.
 9. A method as in claim 7, wherein the devicemeasurement is the acoustic output amplitude of thecontroller-transmitter.
 10. A method as in claim 7, wherein the devicemeasurement is efficiency of energy transmission from thecontroller-transmitter to the receiver-stimulator.
 11. A method as inclaim 1, wherein the target tissue location is held constant at apredetermined site while only the remote tissue location is varied. 12.A method as in claim 1, wherein the remote tissue location is heldconstant at a predetermined site while only the target tissue locationis varied.
 13. A method as in claim 1, wherein both the target tissuelocation and the remote tissue location are varied.